RMD Open最新文献

Objective: To describe the joint manifestations associated with clonal haematopoiesis and to compare patients with and without VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.

Methods: Patients screened for UBA1 mutations between December 2019 and January 2023 in 7 Normandie (France) hospitals were recruited retrospectively.

Results: Thirty patients with a haematological disorder associated with dysimmune manifestations were included: 17 (57%) without UBA1 mutations (non-VEXAS) and 13 (43%) with UBA1 mutations (VEXAS). Thirteen (77%) non-VEXAS patients had joint involvement (arthralgia/arthritis), compared with 4 (31%) VEXAS patients (p value: 0.016). Unsupervised clustering using hierarchical clustering identified two clusters. Cluster 1 (14 patients) had more joint involvement (93% vs 25%, p value: 0.001), less UBA1 mutation (14% vs 69%, p value: 0.008), pulmonary involvement (7% vs 50%, p value: 0.017), chondritis (0% vs 50%, p value: 0.003) and unprovoked venous thrombosis (7% vs 43%, p value: 0.039) than cluster 2 (16 patients). Cluster 1 had more ASXL1 mutations (21% vs 0%).

Conclusion: Joint involvement was more frequent in patients with clonal haematopoiesis and dysimmune manifestations unrelated to VEXAS syndrome.

Objectives: To compare the spondyloarthritis (SpA) specific universal health utility estimation from the ASAS health index (U-ASAS-HI) with the generic EuroQol-5D-3L (EQ-5D-3L) utility among SpA subtypes and to understand the contribution of health-, personal- and country-level factors to the U-ASAS-HI.

Methods: Ancillary analysis of the ASAS-PERipheral involvement in SpondyloArthritis (PerSpA) study including patients who completed both ASAS-HI and EQ-5D-3L. Correlations between U-ASAS-HI and EQ-5D-3L were tested overall and by subtype (axial SpA, peripheral SpA and psoriatic arthritis (PsA)). Health and contextual determinants of U-ASAS-HI were evaluated using multivariable linear mixed-effects models with country as level.

Results: 4158 patients were included, mean age 44 (SD:13) and 61% male. Mean U-ASAS-HI was 0.44 (SD:0.30) and mean EQ-5D-3L was 0.71 (SD:0.21), with numerically minor differences between subtypes. Correlations between U-ASAS-HI and EQ-5D-3L were consistently strong between subgroups (range 0.74-0.76). Linear mixed-effects modelling showed health outcomes, including disease activity (axial spondyloarthritis disease activity score; β=-0.030, 95% CI -0.038 to -0.021), physical function (bath ankylosing spondylitis functional index; β=-0.044, 95% CI -0.048 to -0.041), anxiety/depression (EQ-5D-3L q5; β=-0.147, 95% CI -0.160 to -0.134) and fibromyalgia (fibromyalgia rapid screening tool; β=-0.068, 95% CI -0.083 to -0.053) were strong predictors of lower U-ASAS-HI. Additionally, female gender, PsA subtype, axial involvement, fatigue and having no employment were associated with lower U-ASAS-HI while older age and university education were associated with higher U-ASAS-HI. The random-effects model indicated an intraclass correlation coefficient of 6% in total variance attributable to differences between countries.

Conclusion: The universal U-ASAS-HI captures the broad range of aspects relevant to valuing SpA health states across SpA subtypes. The lower absolute values of U-ASAS-HI reflect the wider disutility associated with SpA.

Objective: Interstitial lung disease (ILD) represents the most common and severe organ manifestation observed in patients diagnosed with connective tissue diseases (CTDs). The aim of this retrospective cross-sectional study was to identify clinical risk factors such as pulmonary symptoms, age, gender, laboratory and pulmonary function test (PFT) parameters associated with the extent of ILD as measured by artificial intelligence-based quantification of pulmonary high-resolution computed tomography (AIqpHRCT).

Methods: We included patients with a CTD-ILD diagnosis; all underwent PFT and HRCT, and pulmonary symptoms and signs of inflammation were also documented. AIpqHRCT was used to quantify lung volumetry and ILD features including ground glass opacities (GGO), reticulations, high-attenuation lung volume (HAV), emphysema and overall extent of ILD. Finally, 76 CTD-ILD patients were eligible for regression analysis, in order to evaluate the influence of clinical parameters on ILD extent.

Results: The reduction of diffusing capacity of the lung for carbon monoxide (DLCO), total lung capacity (TLC) and elevated inflammation parameter was significantly associated with the extent of GGO, reticulations, HAV and overall extent of ILD. Pulmonary symptoms, age and forced vital capacity were not associated with the extent of ILD quantified by AIqpHRCT.

Conclusion: The study presented that DLCO and TLC were predictive for the CTD-ILD severity. Consequently, our findings suggest the performance of PFT, including DLCO for all patients with CTD. In the case of reduced DLCO and TLC, further diagnostics, including HRCT, are necessary.

Objective: To investigate the association between peripheral disease activity and pre-eclampsia, gestational hypertension, preterm birth and fetal growth in women with psoriatic arthritis (PsA).

Methods: Data from a Norwegian nationwide register (RevNatus) were linked with data from the Medical Birth Registry of Norway (MBRN). Cases were singleton births in women with PsA with available disease activity assessment (n=109) included in RevNatus 2010 to 2019. Singleton births registered in MBRN during the same decade served as population controls (n=575 798). Disease activity was assessed by Disease Activity Score based on 28 joints using C reactive protein (DAS28-CRP) in 2nd and 3rd trimester. Active PsA was defined as DAS28-CRP≥2.6 (n=34) and inactive PsA as DAS28-CRP<2.6 (n=75).

Results: Pre-eclampsia was most frequent in women with active PsA (3/34, 8.8%), with a risk difference of 6.1% (95% CI 0.3 to 20.3, p=0.036) compared with population controls (2.6%). Gestational hypertension occurred in 2/34 (5.9%) of women with active PsA, with a risk difference of 4.2% (95% CI 0.0 to 17.4, p=0.065) compared with population controls (1.7%). Pre-eclampsia and gestational hypertension occurred in similar proportions in women with inactive PsA (1.3%, p=0.59 and 2.7%, p=0.24, respectively) and population controls. The occurrence of preterm birth and abnormal fetal growth was comparable in cases and population controls.

Conclusion: Hypertensive disorders of pregnancy occurred more often in women with active, but not inactive PsA. We found no increased risk for preterm birth or abnormal fetal growth in women with PsA.

Objective: To summarise the measurement properties of instruments used to assess fatigue in people with rheumatic and musculoskeletal diseases (RMDs).

Methods: A systematic review (SR) of measurement properties was conducted in children, adolescents/young adults and adults with RMDs, following Joanna Briggs Institute and COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) guidelines. Searches were performed in Medline, Embase, CINAHL and Cochrane Library. Risk of bias assessment, data extraction and synthesis were conducted independently by two reviewers. Instruments were assessed according to Outcome Measures in Rheumatology (OMERACT) criteria.

Results: Out of 16 657 records, 109 articles underwent full-text review, and 60 met inclusion criteria. These studies evaluated the psychometric properties of 27 instruments. Most studies focused on construct validity (54/60, 90%) and intermethod reliability (45/60, 75%), with an overall low risk of bias. In contrast, test-retest reliability (13/60, 21.7%) and responsiveness (14/60, 23.3%) were less frequently assessed, but also with an overall low risk of bias. Evidence regarding clinical trial discrimination and thresholds of meaningful change was limited or absent, indicating the need for further research in these domains. Only five instruments-the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue, the 36-Item Short Form Survey Instrument (SF-36) Vitality, the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the BRAF Numerical Rating Scales (BRAF-NRS) and the Fatigue Severity Scale (FSS)-were rated as valid, reliable and low risk of bias, fulfilling OMERACT endorsement criteria.

Conclusions: This SR comprehensively supports the use of several well-validated instruments to assess fatigue, particularly FACIT-Fatigue, SF-36 Vitality, BRAF-MDQ, BRAF-NRS and FSS, in both clinical and research settings.

Prospero registration number: CRD42024507112.

Background: Disappointing outcomes in Sjögren's disease (SjD) trials underscore the need for reliable, sensitive endpoints. Histological assessment holds promise, but a minimally invasive, repeatable method for salivary gland tissue sampling is lacking.

Objectives: To evaluate the feasibility, safety and tissue adequacy of ultrasound-guided core needle biopsy (US-guided CNB) of the parotid gland and explore its role for facilitating histology-driven stratification and precision medicine.

Methods: In the Belgian Sjögren's Syndrome Transition Trial, 66 patients (64 without gland swelling) underwent US-guided CNB. US was evaluated using OMERACT (Outcome Measures in Rheumatology Clinical Trials). and Hocevar scoring. Histopathology included assessment of focus score, B cell predominance (CD20>CD3), follicular dendritic cell networks (CD21), plasma cells (CD138), lymphoepithelial lesions (CK7/CK14) and FcRL4+ B cells. Pain was assessed using a visual analogue scale (VAS) from 0 to 10. Findings were matched with clinical data.

Results: Mean VAS pain scores were 2.7 (SD=2.77) during biopsy and 1.9 (SD=2.33) in the 3 days before the follow-up call at day 14. No major complications occurred, and 82% of patients were willing to repeat the procedure. Adequate tissue was retrieved in 62/66 cases. Patients showed histological heterogeneity and were, as proof of concept, stratified into mild, moderate and severe histological involvement. Histological severity correlated with ultrasound scores (p<0.01) and not with traditional outcome measures (European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient-Reported Index dryness and European Alliance of Associations for Rheumatology Sjögren's Syndrome Disease Activity Index).

Conclusion: US-guided CNB is safe, well-tolerated and yields adequate tissue. Beyond diagnostics, it might facilitate histology-driven patient stratification and advance precision medicine for SjD.

Background: Mixed connective tissue disease (MCTD) has long been debated as an early nonspecific phase/symptom of differentiated connective tissue diseases (dCTD), similarly to interstitial pneumonia with autoimmune features (IPAF) and very early diagnosis of systemic sclerosis (SSc) (VEDOSS).

Objective: We aimed to evaluate the predictive value of IPAF, VEDOSS and dCTD classification criteria variables in MCTD patients.

Methods: We conducted an observational study within the French MCTD cohort. IPAF, VEDOSS and current dCTD classification criteria were used to classify patients.

Results: Three hundred and twenty-four MCTD patients were included and followed for 8 (3.3-13) years. Among them, 111 (34.3%) progressed into a dCTD, that is, 50 (15.4%) SSc, 40 (12.3%) systemic lupus erythematosus (SLE) and 11 (3.4%) Sjögren's disease. At diagnosis, 38 (11.7%) patients fulfilled IPAF criteria, among which 15 (39.5%) progressed into a dCTD (vs 75 (26.2%) in patients who did not fulfil IPAF criteria; p=0.09). At diagnosis, 293 (90.4%) patients fulfilled VEDOSS criteria but did not progress significantly more frequently to SSc than MCTD patients without VEDOSS criteria (46 (15.7%) vs 4 (12.9%); p=0.8). At baseline, SSc classification criteria did not predict evolution toward SSc, whereas antiphospholipid antibodies and low C3 and/or C4 were predictive of an evolution toward SLE (p=0.01 and p=0.04, respectively).

Conclusion: At MCTD diagnosis, fulfilment of IPAF and/or VEDOSS criteria was not predictive of evolution toward SSc, whereas antiphospholipid antibodies and low C3 and/or C4 were predictive of an evolution toward SLE. This suggests that MCTD patients should be excluded from IPAF and VEDOSS.

Objectives: Patients with primary Sjögren's disease (SjD) have an increased risk of B cell lymphoma. The aim of this study was to determine serum protein biomarkers for lymphoma development and to advance our understanding of the functional mechanisms underlying lymphomagenesis in SjD.

Methods: Patients with SjD and incident, current lymphoma (n=18) with serum sampled before treatment and at 6, 12 and 24 months of follow-up, and four patients sampled 1-5 years before lymphoma diagnosis (pre-lymphoma) were included. SjD without lymphoma (n=21), SjD with historical lymphoma (n=6) and healthy blood donors (n=39) served as controls. Differentially expressed proteins between groups were analysed using the Olink Target 96 Immuno-Oncology panel applying a false discovery rate (FDR) adjusted p value of 0.05. Protein-derived interferon activation scores (pIFN scores) were calculated.

Results: We determined 18 differentially expressed proteins in SjD with incident lymphoma compared with both SjD without lymphoma and healthy controls. Among the top upregulated proteins were TNFSF14, FGF2, IL8, CD40 and CXCL13, where CXCL13 was the only protein with decreased levels at follow-up. We also observed upregulated expression of CD40 in the SjD pre-lymphoma group compared with SjD without lymphoma and healthy controls. All SjD patient groups presented elevated pIFN scores compared with healthy controls, where SjD sampled pre-lymphoma showed the most distinct IFN activation.

Conclusions: We identified altered protein expression and an increased IFN system activation in SjD with incident lymphoma and pre-lymphoma. This knowledge may contribute to earlier detection of high-risk patients, identification of therapeutic targets and may ultimately improve SjD patient outcomes.

Background: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated 2-year efficacy in non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA (r-axSpA) phase III studies.

Objective: Assess the impact of BKZ on peripheral manifestations to week 104 of those studies.

Methods: BE MOBILE 1 (nr-axSpA) and 2 (r-axSpA) each comprised a 16-week double-blind, placebo-controlled period, then all received BKZ 160 mg every 4 weeks for 36 weeks. Patients not meeting withdrawal criteria could enter a combined open-label extension. We report change in enthesitis (Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)) in patients with baseline MASES>0, peripheral arthritis (swollen joint count (SJC)/Disease Activity Index for Psoriatic Arthritis (DAPSA)) in patients with baseline SJC>0 and proportions achieving DAPSA disease states to week 104. Resolution of enthesitis (MASES=0)/arthritis (SJC=0) is reported to week 104 for those with baseline enthesitis/arthritis. We also report associations between peripheral manifestation resolution (MASES=0/SJC=0) and week 104 clinical outcomes in those with baseline enthesitis/arthritis.

Results: At baseline, 186/254 (73.2%) and 88/254 (34.6%) patients with nr-axSpA had enthesitis (MASES>0) and arthritis (SJC>0), respectively, compared with 199/332 (59.9%) and 66/332 (19.9%) patients with r-axSpA. Pooled BKZ/placebo-randomised patients with enthesitis (nr-axSpA/r-axSpA) showed average MASES improvement from 4.8/4.3 (baseline) to 1.6/1.3 (week 52) and 1.6/1.0 (week 104). Pooled BKZ/placebo-randomised patients with arthritis showed average SJC improvement from 4.0/4.5 (baseline) to 1.2/0.7 (week 52) and 0.9/0.6 (week 104). Over 60% of patients achieved DAPSA low disease activity/remission by week 52. Over 40%/60% patients achieved resolution of enthesitis (MASES=0)/arthritis (SJC=0) at week 104; enthesitis resolution was associated with larger improvements in week 104 clinical outcomes for patients with r-axSpA.

Conclusion: BKZ resulted in sustained improvements in peripheral manifestations to 2 years across the full disease spectrum of axSpA.

Background: Data on cardiorespiratory fitness (CRF) in psoriatic arthritis (PsA) are scarce. This study aimed to determine the CRF level in patients with PsA and to examine the relation between CRF and disease parameters, cardiometabolic risk profile as well as patient-reported outcome measures (PROMs).

Methods: In this cross-sectional study, CRF was measured as peak oxygen uptake (VO₂peak) during an incremental maximal cardiopulmonary exercise test and compared with reference charts of the general population using the one-sided t-test. Multivariable linear regression models were built to evaluate the associations between VO₂peak (mL/min/kg, log-transformed) and disease parameters, cardiometabolic risk parameters and PROMs. Statistical significance was defined as p<0.05 with application of Holm-Bonferroni correction in regression analysis (expressed as p*).

Results: In 80 patients with PsA (41% females, mean age 51 years (SD=11)), mean VO₂peak was 26.03 mL/min/kg (SD=7.56) and significantly decreased compared with the physically active reference population (mean 74.01% (SD=19.19), p<0.001) with 41% having an impaired CRF. In the final multivariable linear regression model, adjusted for age and sex, disease activity (Psoriatic Arthritis Disease Activity Score: β=-0.2757, p*=0.009), waist-hip ratio (β=-0.4193, p*<0.001), patient-reported disease impact (Psoriatic Arthritis Impact of Disease 12-item questionnaire: β=-0.2385, p*=0.015), and moderate-to-vigorous physical activity during commuting and leisure time (minutes/week: β=0.1702, p*=0.015) were significantly associated with VO₂peak (adjusted R²=0.71).

Conclusions: The CRF level of patients with PsA was significantly decreased compared to a physically active population with 41% having an impaired CRF. A lower CRF level was substantially associated with impaired disease control, unfavourable body composition, lower self-reported physical activity as well as with higher patient-reported disease impact.